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Management of diastolic heart failure

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Management of diastolic heart failure Management of diastolic heart failure Presentation Transcript

  • CASE REPORT Management of Diastolic Heart Failure:What is the Recent Results in Clinical Trial 報告學生:陳秋縈 指導老師:李貽恆醫師 報告日期:2012/11/13
  • Patient profile Name 吳○○ Admission date 2012/10/18 Age 79 Allergy history NKDA Gender female Social history Smoking: (-) HT/BW 168cm/62.3kg Drinking: (-) Betel nut: (-) BMI 22 Drug abuse: (-) Past history Regular medication • Hypertension • Amlodipine 5mg PO QD • Persistent atrial fibrillation • Furosemide 20mg PO QOD • Hyperuricemia • Aspirin EM 100mg PO QD • Impaired glucose tolerance • Benzbromarone 50mg PO QD Chief complaint • Productive cough and shortness of breath for 2 weeks • Mild fever up to 37.3°C in recent days2
  • History of present illness • Intermittent exertional dyspnea for several years LOCAL CLINIC PRESCRIPTION • Long term follow up in local clinic • Olmesartan /Amodipine 20mg/5mg PO QD • Bumetanide 0.5mg QD4/12 • Visit NCKUH CV OPD • Digoxin 0.125mg PO QD • Arrange further examination • Aspirin EM 100mg PO QDAC • Benzbromarone 50mg PO QD4/23 • CXR: Cardiomegaly, atherosclerosis of the aorta OPD PRESCRIPTION • ECG: AF, VPC • Amlodipine 5mg PO QD • Furosemide 20mg PO QOD • Echocardiography: • Aspirin EM 100mg PO QDAC Dilated RA, LA and LVH • Benzbromarone 50mg PO QD Adequate global LV systolic performance Mild MR and TR with mild pulmonary HTN10/18 • Suffered from productive cough and intermittent low grade fever for 2 weeks • Dyspnea, transferred to ER from OPD 3
  • Physical examination • VITAL SIGN TPR: 37.7/85/20 BP: 141/78 mmHg SpO2: 92% • NECK: JVE(+) • CHEST: crackles over right lower lung • HEART: irregular heart beats, grade III/IV pansystolic murmur over apex • EXT: bilateral legs pitting edema 3+ECG • Af with RVRCXR • Cardiomegaly • Patchy consolidatoin and infiltrations over both lungs  Suspect pneumonia or lung edema4
  • Lab data Normal Normal 10/18 10/18 range rangeALBUMIN 3.5-5 4.1 g/dL WBC 3.2-9.2 9.8 10^3/μL CREA 0.6-1.2 1.16 mg/dL Hb 11.6-14.8 10.8 g/dL eGFR 45 Plt 151-366 183 10^3/μL ALT 0-54 15 U/L Blast 0 % CK 30-135 154 U/L Pro 0 % NA 135-148 145 mmol/L Myelo 0.5 % K 3.5-5 4.8 mmol/L Meta 0 % GLU.P.C. 80-140 144 mg/dL Band 1 % CK-MB <2.9 3.62 ng/mL Seg 43-64 79.5 % hsTnT 0.025 ng/mL Eos 0-6 0 %NTproBNP <125 12956 pg/mL Baso 0-1 0 % Mono 3-9 8 %Impression Lymph 27-47 11 %• HF with AE, favor infection induced• Af with RVR Aty-lym 0 %• HTN 5 NRBC 0 /Count WBCs
  • Hospital courseDate Event Management10/18 • BT: 37.7, cough, dyspnea • S/C & gram stain, B/C x 2 sets • CXR : patchy consolidatoins and infiltrations • Acetaminophen 500mg16:00 • WBC: 9.8 (103/μL), Seg: 79.5%, band:1% Q6HPRN if BT>38.3at ER Suspect CAP • Ceftriaxone inj 1g IVD Q12H • Legionella & pneumococcus Ag (urine): (-) • Levofloxacin 500mg PO • PCT: (-) QDAC • SOB, orthopnea • O2: 3L/min • BP: 141/78 mmHg, SpO2: 92% • Furosemide 40mg IVP STAT • IRHB, JVE(+), crackles over right lower lung, • Digoxin 0.25mg in NS 50ml lower leg pitting edema IVD 30min STAT • CXR: cardiomegaly • ECG: Af with RVR • NTproBNP: 12956 pg/mL Suspect HF with AE 6
  • Hospital course Date Event Management 10/18 HF with AE, favor infection related • Diet: 限鹽 5g/day, 限水1500ml/day Echocardiography report HTN previous under amlodipine Dilated LA, LV, RA • Shift amlodipine to 18:00 • Scr:Adequate LV systolicmmol/L 1.31 mg/dL, K:4.8 performance Valsartan 80mg PO QD after • Furosemide 40mg PO BID Moderately-severe posterior-eccentric MR (3+) Persistent Afadmission Gout Moderately-severe TR (3+) history • Isosorbide DN 5mg PO TIDAC Normal LV filling pressure, mean E/E=7.7 (<8) 0.125mg PO QD • Digoxin Af with occasional VPCs • Aspirin EM 100mg QD LVEF: 61.1% • Benzbromarone 50mg PO QD 10/20 • Echocardiography report • Furosemide 40mg PO QD  HF with Preserved Ejection Fraction (HFPEF) • SOB improved, BW↓, I/O↑ 10/18 10/19 10/20 BW (kg) 62.3 61.25 60.8 I/O (ml) -390 -650 +40 7 LVEF: left ventricular ejection fraction
  • Hospital courseDate Event Management10/21 10/18 10/18 10/21 • Keep Valsartan use 10/22 Scr (mg/dL) 1.16 0.82 K (mmol/L) 4.8 3.610/22 • SOB improved, no orthopnea, • Valsartan 160mg PO QD less cough, less edema • Furosemide 20mg PO QD • F/U lab no leukocytosis • DC Ceftriaxone WBC: 4.5 (103/μL), Seg:61.8% • CXR: complete resolution of consolidation10/23 • TPR: 36.8/60/20 • Discharged and OPD F/U Discharge Order • BP:113/85 mmHg • Valsartan 160mg PO QD • Stable condition • Furosemide 20mg PO QD • Isosorbide DN 5mg PO TIDAC • Digoxin 0.125mg PO QD • Aspirin EM 100mg PO QDAC • Benzbromarone 50mg PO QD 8 • Levofloxacin 500mg PO QDAC x 4days
  • Summary of our patient discharge Drug 10/18 10/19 10/20 10/21 10/22 10/23 order Ceftriaxone 100mg IVD q12h CAP Levofloxacin 500mg qdAC Acetaminophen 500mg q6h prn Isosorbide DN 5mg tidAC Scr 1.16 mg/dL Scr 0.82 mg/dL K 4.8 mmol/L K 3.6 mmol/L HF Valsartan 80mg qd 160mg QD Furosemide 40mg bid 40mg QD 20mg QD Digoxin 0.125mg qd Af Aspirin EM 100mg qdHyperu-ricemia Benzbromarone 50mg qd BW(kg) 62.3 61.25 60.8 60.5 60.4 59.7 9 I/O (ml) -390 -650 +40 +450
  • Outline Diastolic heart failure (DHF)  Definition and diagnosis criteria  Epidemiology  Pathophysiology  Clinical Manifestations  Management  Recent results in clinical trials Case discussion Take home message10
  • Heart failure A complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.  Systolic heart failure  Diastolic heart failure11 ACC/AHA Practice Guidelines
  • Diastolic Heart Failure (DHF)Also called:• Diastolic dysfunction• Heart failure with preserved ejection fraction (HFPEF)• Heart failure with normal ejection fraction (HFNEF)
  • Definition Vary with no global consensus A clinical syndrome  Signs or symptoms of heart failure  Congestion, low perfusion  Normal or near normal left ventricular systolic function  Variably defined as an LVEF >40%, >45%, or >50%  Evidence of diastolic dysfunction  Abnormal left ventricular relaxation, impaired filling , myocardium stiffness LVEF: left ventricular ejection fraction 1. Galderisi M. Cardiovasc Ultrasound. 2005 Apr 4;3:9.13 2. Aurigemma GP, Gaasch WH. N Engl J Med. 2004;351(11):1097.
  • Diagnostic Criteria Clinical evidence of HF: Clear clinical presentation of HF or Framingham or Boston criteria If uncertain: Plasma BNP or NT-proBNP or chest x-ray Systolic HF or cardiopulmonary exercise testing Diastolic HF LVEF < 50% LVEF ≥ 50% Supportive evidence: Supportive evidence: • Concentric LVH or remodeling • Eccentric LVH or remodeling • Left atrial enlargement in absence of AF • Echo Doppler or catheter evidence of diastolic dysfunction Exclusions: • Non-myocardial disease Exclusions: • Non-myocardial disease14 Adapted from Yturralde FR. Prog Cardiovasc Dis 2005;47:314-19 2009 Focused Update: ACCF/AHA Heart FailureGuidelines
  • Epidemiology 50% of patients with HF has normal LVEF Increasing prevalence Secular Trends in the Prevalence of HF-PEF DHF SHF Owan T, et al. NEJM. 2006;355:251-915
  • Mortality: SHF vs. DHF Varies with cohort studied  Differences in definition used to diagnose, co-morbidities present, composition of the populations studied HR 1.13; 95%CI 0.94-1.36; P=0.18 No significant difference16 Bhatia RS. NEJM. 2006;355:260-9 Owan T, et al. NEJM. 2006;355:251-9
  • Patient Characteristics: SHF vs. DHF SHF DHF older female  lower    17 Owan T, et al. NEJM. 2006;355:251-9
  • Etiology Major causes Precipitating factors  Hypertension  Excess salt intake  Coronary heart disease  Exercise  Diabetes  Anemia  Cardiomyopathy  Infection  Tachycardia  Arrhythmia18
  • Pathophysiology Risk factors HTN, CAD, DM, Cardiomyopathy, Obesity, Aging Abnormalities of active relaxation Passive stiffness of myocardium Impaired Left ventricular filling capacity19 Mandinov L, Eberli FR, Seiler C, Hess OM. Cardiovasc Res. 2000 Mar;45(4):813-25.
  • Clinical Manifestations Extravascular water ↑ Tissue perfusion ↓  Dyspnea  Cool arms and legs  Elevated jugular venous  Sleepy, obtunded pressure  Hypotension  Pulmonary rales  Worsening renal function  Edema20
  • Management  Limited evidence, no standard treatment regimen Level of Evidence C: Only consensus opinion of experts, case studies, or standard of care.ACC/AHA HF PRACTICE GUIDELINE RECOMMENDATIONS Class Level• Control systolic and diastolic hypertension in accordance with published guidelines I A• Use diuretics to control pulmonary congestion and peripheral edema I C• Coronary revascularization in patients with CAD in whom ischemia is judged to be IIA C having adverse effect on cardiac function• In patients with atrial fibrillation − Control ventricular rate I C − Restoration and maintenance of sinus rhythm might improve symptoms IIB C• Use of beta-adrenergic blocking agents, ACEIs, ARBs, or calcium antagonists in patients IIB C controlled hypertension might be effective to minimize symptoms of HF• Usefulness of digitalis to minimize symptoms is not well established IIB C 21 Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. Circulation. 2009;119:e391-e479
  • Management Principle Target on • Symptom reduction • Causes and risk factors Pharmacotherapy • Possibly •beneficial effect on pathophysiology ACEI/ARB • Aldosterone antagonist • Beta blocker Goal • CCB • Diuretic • Control hypertension • Other: Digoxin, state • Reduce the congestive Statin, Vasodilator Nonpharmacologic therapy • Treat and prevent myocardial ischemia • Lifestyle modification • Maintain atrial contraction and prevent tachycardia • Promote regression of hypertrophy and fibrosis*22 1. Koprowski A, Gruchala M, Rynkiewicz A. Curr Opin Cardiol. 2009 Mar;24(2):161-6. *thioretical benefit 2. Aurigemma GP, Gaasch WH. N Engl J Med. 2004 Sep 9;351(11):1097-105.
  • SHF vs. DHF Systolic heart failure Diastolic heart failure Impaired myocardial contractility Impaired relaxation and filling Pathophysiology Dilated heart Hypertrophied heart Ejection Fraction Reduced Normal Signs and Symptoms SimilarMortality and Morbidity No significant differenceBNP/NT-proBNP Levels More elevated Less elevated Older WomanPatient Characteristics Prior myocardial infarction Obesity Hypertensive Atrial fibrillation Evidence 23 Well Poor Supported Treatment
  • What is the recent results in clinical trial
  • Completed trials for HF with preserved EF Trial Drug Patient Follow-up PEP-CHF • n=850 Perindopril 26.2 mo 2006 • EF ≥ 40% VALIDD • n=384 Valsartan 38 wk 2007 • EF>50% I-PRESERVE • n=4128 Irbesartan • EF ≥ 45% 49.5 mo 2008 CHARM-Preserved • n = 3023 Candesartan 36.6 mo 2003 • EF > 40% Cochrane Syst Rev • LVEF>40%, n=7151 ARB Meta analysis 2012 • LVEF≤40% , n=3766 • n = 7154 OPTIMIZE – HF Retrospective β-blockers • EF > 40% 2009 cohort • Naï to β-blockers veDIG trial (ancillary group) • N= 988 Digoxin 37 mo 2006 • EF > 45% 1. Lancet. 2003 Sep 6;362(9386):777-81 1. Eur Heart J. 2006 Oct;27(19):2338-45 2. Cochrane Database Syst Rev.2012 Apr 18;(4)25 2. Lancet 2007; 369:2079. 3. J Am Coll Cardiol. 2009;53(2):184 3. N Engl J Med. 2008 Dec 4;359(23):2456-67 4. Lancet. 2003 Sep 6;362(9386):777-81
  • ACEI PEP-CHF: Perindopril Perindopril in Elderly People with Chronic Heart Failure Eur Heart J. 2006 Oct;27(19):2338-45 N=850, age≥ 70y (median age 75 y) Patient with diastolic dysfunction, exclude LVEF < 40% hospitalized for a cardiovascular cause within previous 6moIntervention Perindopril titrate to 4mg QD vs. Placebo Primary: Outcome All-cause mortality or hospitalization for HF Follow-up mean 26.2 mo (range 12-30) 26 Cleland JG, Tendera M, Adamus J, et al. Eur Heart J. 2006 Oct;27(19):2338-45.
  • PEP-CHF: PerindoprilResultsPerindopril vs. Placebo•Reduce unplanned heart failure related hospitalization at 1 year 8% vs. 12.4% (p = 0.033, NNT 23)•All-cause mortality or hospitalization for HF 23.6% vs. 25.1% (HR 0.92; 95% CI 0.70 to 1.21; p = 0.545)27 Cleland JG, Tendera M, Adamus J, et al. Eur Heart J. 2006 Oct;27(19):2338-45.
  • ARB VALIDD (Valsartan in Diastolic Dysfunction) Effect of angiotensin receptor blockade and antihypertensive drugs on diastolicfunction in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet. 2007 Jun 23;369(9579):2079-87 n = 384, History of stage 1 or 2 essential HTN, LVEF>50% Patient Give antihypertensive agents not inhibit RAA system (diuretic, βb, ccb, α blocker) BP target under 135/80mmHgIntervention Valsartan titrate to 320mg/day vs. Placebo Change in diastolic relaxation velocity Outcome Change in BP Follow-up 38 wk Valsartan vs. Placebo • Reduce BP and increase diastolic relaxation velocity not significant between groups Results significantly from baseline(p<0.0001)  Valsartan may not improve diastolic function beyond antihypertensive effect  Lowering BP improves diastolic function irrespective of the type of antihypertensive agent used 28 Solomon SD, Janardhanan R, Verma A, et al. Lancet. 2007 Jun 23;369(9579):2079-87
  • ARBI-PRESERVE: Irbesartan Irbesartan in patients with heart failure and preserved ejection fraction N Engl J Med. 2008 Dec 4;359(23):2456-67 n = 4128, mean age 72 y EF ≥ 45% Patient NYHA class II-IV symptoms Hospitalized for HF during last 6 mo or persist class III or IV symptoms Irbesartan titrate to 300mg/day vs. PlaceboIntervention Mean dose 275mg/day Primary: Outcome All-cause death or hospitalization for a cardiovascular cause Follow-up mean 49.5 mo Irbesartan vs. Placebo • 36% vs. 37% (HR 0.95; 95% CI 0.86 to 1.05; p = 0.35) Results No significant differences between groups  Irbesartan does not reduce mortality or hospitalization in HFPEF29 Massie BM, Carson PE, McMurray JJ, et al. N Engl J Med. 2008 Dec 4;359(23):2456-67
  • ARBCHARM-Preserved: Candesartan Effects of candesartan in patients with chronic heart failure and preserved left- ventricular ejection fraction: the CHARM-Preserved Trial Lancet. 2003 Sep 6;362(9386):777-81 n = 3023, mean age 67 y EF > 40% Patient NYHA class II-IV for at least 4 wks hospital admission for cardiovascular causes Candesartan titrate to 32mg/day vs. PlaceboIntervention Mean dose at 6 mo: 25mg/day Primary: Outcome cardiovascular death or hospital admission for HF Follow-up mean 36.6 mo30 Yusuf S, Pfeffer MA, Swedberg K, et al. Lancet. 2003 Sep 6;362(9386):777-81.
  • ARBCHARM-Preserved: CandesartanResultsCandesartan vs. Placebo• Reduce hospital admission for HF 15.9% vs. 18.3% (p=0.047, NNT 42)• Cardiovascular death or hospital admission for HF 22% vs. 24% (adjusted HR 0.86; 95% CI 0.74 to 1.00; p = 0.051) 31 Yusuf S, Pfeffer MA, Swedberg K, et al. Lancet. 2003 Sep 6;362(9386):777-81
  • ARB Angiotensin receptor blockers for heart failure Cochrane Database Syst Rev. 2012 Apr 18;4:CD003040. Study design: Systemic review of RCTs Objective: Compare ARBs with ACEIs or placebo on mortality, morbidity and withdrawals due to adverse effects in patients with symptomatic HF (NYHA Class II to IV) (subgroup: LVEF>40%, LVEF≤40% ) Results: 11 trials with 11,794 patients compared ARBs vs. placebo 2 trials in 7,151 patients with LVEF > 40% included  Candesartan (CHARM-preserved trial)  Irbesartan (I-PRESERVE trial)32
  • ARBs vs. placebo in LEVF > 40% ARBTotal Mortality No significant differencesTotal Hospitalizations No significant differences 33 Cochrane Database Syst Rev.2012 Apr 18;(4)
  • ARB ARBs vs. placebo in LEVF > 40%Hospitalisations for Heart Failure ARB might reduce hospitalization for heart failure but not total hospitalizations or mortality in patients with symptomatic HF and EF > 40% 34 Cochrane Database Syst Rev.2012 Apr 18;(4)
  • β-blockersOPTIMIZE – HF: β-blockers Clinical effectiveness of beta-blockers in heart failure: findings from the OPTIMIZE-HF Registry. Am Coll Cardiol. 2009;53(2):184Study design A retrospective cohort study Objective Examine associations between initiation of β-blocker therapy and outcomes OPTIMIZE-HF(Organized Program to Initiate Lifesaving Treatment inData source Hospitalized Patients With Heart Failure) Centers for Medicare and Medicaid Services (CMS) N= 7154 (LVSD: 3001; preserved systolic function: 4153), age>65y Patient hospitalized with HF Naï to β-blockers veIntervention newly initiated β-blocker vs. no β-blocker Outcome Mortality, rehospitalization, and a combined mortality–rehospitalization 35 Hernandez AF, Hammill BG, OConnor CM et al. J Am Coll Cardiol. 2009;53(2):184.
  • β-blockersOPTIMIZE – HF: β-blockers SHF Reduced mortality and rehospitalization rates No improvement in mortality or rehospitalization DHF36 Hernandez AF, Hammill BG, OConnor CM et al. J Am Coll Cardiol. 2009;53(2):184.
  • Digoxin DIG trial (ancillary group): digoxinEffects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006;114(5):397 n = 988, mean age 67 y EF > 45% Patient NYHA class I-IV Normal sinus rhythm Most patient were taking ACEI and diuretics Digoxin 0.125, 0.25, 0.375, or 0.5 mg/day vs. Placebo (n= 496) Intervention Mean dose: 0.25mg/day Outcome HF hospitalization or HF mortality Follow-up mean 37 mo Digoxin vs. Placebo Results • HF hospitalization or HF mortality 21% vs. 24% (HR 0.82; 95% CI 0.63 to 1.07; p = 0.136) 37 Yusuf S, Pfeffer MA, Swedberg K, et al. Lancet. 2003 Sep 6;362(9386):777-81.
  • DigoxinDIG trial (ancillary group): digoxin Digoxin does not reduce morbidity or mortality in patients with DHF and normal sinus rhythm receiving ACEI and diuretics38
  • SpironolactoneOngoing trials Trial of Aldosterone Antagonist Therapy in Adults With Preserved Ejection Fraction Congestive Heart Failure (TOPCAT) Start Date: August 2006 Estimated Completion Date: July 2013 N = 4500 Study design: Randomised Double blind clinical trial Compare: Spironolactone vs. placebo Primary outcome: hospitalization for the management of heart failure and Aborted cardiac arrest39 ClinicalTrials.gov: NCT00094302
  • Case discussion
  • Back to our patient HF with Preserved Ejection Fraction Af HTN41
  • Treatment strategy in our patient Target on • Symptom reduction • Causes and risk factors • Possibly beneficial effect on pathophysiology Current medication • Reduce the congestive state • Furosemide 20mg PO QD • Isosorbide DN 5mg PO TIDAC • Control HTN • Valsartan 160mg PO QD • Control Af • Aspirin EM 100mg PO QDAC • Digoxin 0.125mg PO QD42
  • Diastolic HF with chronic Af LV filling in DHF  Occurs largely in late diastole  More dependent on atrial contraction Shorten Deteriorate Af Tachycardia diastolic HF filling period Rate control in DHF with Af is important!43
  • Control Atrial Fibrillation Current medication: Digoxin 0.125mg PO QD Rate Recommendation: control Consider beta blocker after the patient is stable Start at low dose then titrate as tolerated Drug of choice mg/tab Initial dose Max dosePotential beneficial effect• Heart rate Bisoprolol 5 1.25 mg QD 10 mg QD• Myocardial oxygen demand  Metoprolol SR 100 12.5-25 mg QD 200 mg QD• Blood pressure  -promote regression of LVH 6.25 Carvedilol 3.125 mg BID 25 mg BID 2544
  • Control Atrial Fibrillation Current medication: Digoxin 0.125mg PO QD Rate Recommendation: control Consider beta blocker after the patient is stable Start at low dose then titrate as tolerated Current medication: Aspirin EM 100mg PO QD Score Risk of Recommendation: C CHF 1 thrombosis CHADS2= 3 H HTN 1 A Age ≥75 yrs 1 Suggest warfarin use D DM 1 S2 Stroke or TIA 245
  • Patient education New or worse symptoms of heart failure Breathing Weight Swelling Activity Life style modification  Low salt diet Medication46
  • Take home message Diastolic heart failure • Signs or symptoms of heart failure  Similar with SHF • Normal or near normal left ventricular systolic function  LVEF ≥ 50% • Evidence of diastolic dysfunction  Abnormal relaxation, myocardium stiffness, impaired filling Treatment strategy • Symptom reduction • Causes and risk factors • Possibly beneficial effect on pathophysiology  Control : BP, HR, congestive state, myocardial ischemia47
  • THANKS